Dual HER2 Blockade in Metastatic Breast Cancer
According to the phase III ALTERNATIVE trial, benefits in progression-free survival were shown among postmenopausal women with HER2-positive metastatic breast cancer who received dual HER2 blockade (lapatinib plus trastuzumab) in combination with an aromatase inhibitor. The study was led by Stephen R.D. Johnston, MA, MBBS, FRCP, PhD, of The Royal Marsden Hospital in London and published in the Journal of Clinical Oncology.
“This combination offers an effective and safe chemotherapy-sparing alternative treatment regimen for this patient population,” concluded the investigators.
A total of 355 patients from 29 countries were enrolled from 112 sites. They had received prior endocrine therapy and prior first-line trastuzumab plus chemotherapy. Patients were randomly assigned (1:1:1) to receive lapatinib, trastuzumab, and an aromatase inhibitor; trastuzumab plus an aromatase inhibitor; or lapatinib plus an aromatase inhibitor.
The dual HER2 blockade group showed the greatest benefits, with a median progression-free survival of 11 months versus 5.7 months for the trastuzumab plus aromatase inhibitor group. In addition, the objective response rate was higher in the triple-combination group (31.7%) than in the trastuzumab plus aromatase inhibitor and lapatinib plus aromatase inhibitor groups (13.7% and 18.6%, respectively).
Patients in the triplet-therapy arm experienced more grade 1 and 2 adverse events. However, serious adverse events were similar among all three arms, and treatment-related discontinuation was lower for patients in the triplet-therapy group.